The CXCL12-CXCR4 chemotactic pathway as a target of adjuvant breast cancer therapies.

Abstract

Dose-dense adjuvant breast cancer chemotherapy is a new treatment strategy that aims to improve tumour control by using more frequent cytotoxic dosing together with continuous granulocyte colony-stimulating factor (G-CSF) to minimize neutropaenia. In addition to stimulating neutrophil proliferation, G-CSF mobilizes neutrophils from the bone marrow through proteolytic disruption of the chemokine receptor CXCR4 and its chemotactic ligand CXCL12. As breast cancers also express CXCR4 and oestrogen induces CXCL12, the success of dose-dense treatment could partly reflect inhibition of CXCR4-dependent micrometastatic homing and/or paracrine survival, and suggests a benefit of adjuvant oestrogen suppression for patients with oestrogen-receptor-negative, CXCR4-positive disease.